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106-451: The first Fandorin novel ( The Winter Queen , Russian: Азазель ) was published in Russia in 1998, and the latest and the last one in 2023 ( The Pit , Russian: Яма ). More than 15 million copies of Fandorin novels have been sold as of May 2006, even though the novels were freely available from many Russian websites and the hard copies were relatively expensive by Russian standards. New books in

212-492: A rattling noise as fluid lingers in the throat, but this is not uncomfortable for the affected person. Their hands and feet may cool to the touch, and skin become blotchy or blue due to weaker blood circulation. Many stop eating and drinking, resulting in dry-feeling mouth, which can be aided by moistening the mouth and lips. The person becomes less and less responsive, and eventually the heart and breathing stop. The prognosis of diagnosed prostate cancer varies widely based on

318-500: A "low genre" by the communist officials, both local (such as Igor (Georgy) Vayner and Julian Semenov ), and foreign detective novels have always been avidly coveted. After the collapse of the Soviet Union, many trashy detective novels were published that featured a lot of gore and sex. Akunin's wife, in common with many other Russians, started to enjoy reading this genre of literature. However, she did not want to be seen reading

424-411: A PSMA-targeting drug, each of which is able to detect small metastases more sensitively than alternative imaging methods. For those with metastatic disease, the standard of care is androgen deprivation therapy (also called "chemical castration"), drugs that reduce levels of androgens (male sex hormones) that prostate cells require to grow. Various drugs are used to lower androgen levels by blocking

530-1057: A combination of the disease itself, poor nutrition, and damage to the bone marrow from cancer treatments or bone metastases. Anemia can be treated in various ways depending on the cause, or can be addressed directly with blood transfusions . Organ damage and metastases in the lymph nodes can lead to uncomfortable accumulation of fluid (called lymphedema ) in the genitals or lower limbs. These swellings can be extremely painful, curtailing an affected person's ability to urinate, have sex, or walk normally. Lymphedema can be treated by applying pressure to aid drainage, surgically draining pooled fluid, and cleaning and treating nearby damaged skin. People with prostate cancer are around twice as likely to experience anxiety or depression compared to those without cancer. When added to normal prostate cancer treatments, psychological interventions such as psychoeducation and cognitive behavioral therapy can help reduce anxiety, depression, and general distress. As those severely ill with metastatic prostate cancer approach

636-494: A feature writer for her local Essex paper, the Chigwell Times . She submitted a story narrating a local sports club dinner she had not attended. Because of her absence at the dinner, she did not know that the after-dinner speaker had died midway through the speech, and failed to report it. She was subsequently forced to resign. Rendell met her husband Don Rendell when she was working as a newswriter. They married when she

742-407: A fragment called −2proPSA) and 4K score (measures intact free PSA). Other tests measure blood levels of additional prostate-related proteins such as kallikrein-2 (also measured by 4K score), or urine levels of mRNA molecules common to prostate tumors like PCA3 and TMPRSS2 fused to ERG . Several large studies have found that men screened for prostate cancer have a reduced risk of dying from

848-475: A higher-risk tumor that may require intervention. At least half of men remain on active surveillance, never requiring more direct treatment for their prostate tumors. Those who elect to have therapy receive radiation therapy or a prostatectomy ; these have similar rates of cancer control, but different side effects. Radiation can be delivered by intensity-modulated radiation therapy (IMRT), which allows for high doses (greater than 80 Gy ) to be delivered to

954-415: A history of gonorrhea , syphilis , chlamydia , or infection with various human papillomaviruses . Regular vigorous exercise may reduce one's chance of developing advanced prostate cancer, as can several dietary interventions. Those with a diet rich in cruciferous vegetables (certain leafy greens, broccoli, and cauliflower), fish , genistein (found in soy ), or lycopene (found in tomatoes) are at

1060-663: A history of any cancer. Men with an affected first-degree relative (father or brother) have more than twice the risk of developing prostate cancer, and those with two first-degree relatives have a five-fold greater risk compared with men with no family history. Increased risk also runs in some ethnic groups, with men of African and African-Caribbean ancestry at particularly high risk – having prostate cancer at higher rates, and having more-aggressive prostate cancers that develop at earlier ages. Large genome-wide association studies have identified over 100 gene variants associated with increased prostate cancer risk. The greatest risk increase

1166-472: A low Gleason grade and less-advanced clinical stage tend to have better prognoses. After prostatectomy or radiotherapy, those who have a short time between treatment and a subsequent rise in PSA levels, or quickly rising PSA levels are more likely to die from their cancers. Castration-resistant metastatic prostate cancer is incurable, and kills a majority of those whose disease reaches this stage. Prostate cancer

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1272-425: A man who had died with urinary issues; Adams had a pathologist examine the tumor, providing the first confirmed case of a cancerous tumor in the prostate. The disease was initially rarely described; an 1893 report found only 50 cases described in the medical literature. Around the turn of the 19th century, prostate surgery to relieve urinary obstruction became more common, allowing surgeons and pathologists to examine

1378-976: A reduced risk of symptomatic prostate cancer. Conversely, those who consume high levels of dietary fats, polycyclic aromatic hydrocarbons (from cooking red meats), or calcium may be at an increased risk of developing advanced prostate cancer. Several dietary supplements have been studied and found not to impact prostate cancer risk, including selenium , vitamin C , vitamin D , and vitamin E . Transgender women and gender non-conforming people who have prostates can develop prostate cancer. Those who have undergone gender-affirming hormone therapy or gender-affirming surgery have reduced risk of developing prostate cancer, relative to cisgender men of similar age. Screening tests in this group are complicated, as transgender women may have lower PSA levels than cisgender men due to their reduced testosterone levels. PSA levels greater than 1 ng/mL are generally considered above normal by gender care specialists. Digital rectal exams of

1484-407: A rise in PSA levels, suggesting the tumor or small metastases are growing again. People with high or rising PSA levels are often offered another round of radiation therapy directed at the former tumor site. This reduces risk for further progression by 75%. Those suspected of metastases can undergo PET scanning with sensitive radiotracers C-11 choline, F-18 fluciclovine, and F-18 or Ga-68 attached to

1590-544: A slightly increased risk for developing prostate cancer, as are men who are obese . High levels of blood cholesterol are also associated with increased prostate cancer risk; consequently, those who take the cholesterol-lowering drugs, statins , have a reduced risk of advanced prostate cancer. Chronic inflammation can cause various cancers. Potential links between infection (or other sources of inflammation) and prostate cancer have been studied but none definitively found, and one large study found no link between prostate cancer and

1696-597: A specially made four-poster bed because "I like to feel enclosed." Baroness Rendell's awards include the Silver, Gold , and Cartier Diamond Daggers from the Crime Writers' Association , three Edgars from the Mystery Writers of America , The Arts Council National Book Awards, and The Sunday Times Literary Award. A number of her works (see the section below) have been adapted for film or television. She

1802-406: A tumor can grow large enough to invade nearby organs such as the seminal vesicles or bladder . In advanced tumors, cells can develop the ability to detach from their original tissue site, and evade the immune system . These cells can spread through the lymphatic system to nearby lymph nodes , or through the bloodstream to the bone marrow and (more rarely) other body sites. At these new sites,

1908-573: A tumor that has grown beyond the prostate (T3). CPG 5 is for the highest risk cases: either a T4 tumor, Gleason grade group 5, or any two of the CPG ;4 criteria. No drug or vaccine is approved by regulatory agencies for the prevention of prostate cancer. Several studies have shown 5α-reductase inhibitors to reduce the total incidence of prostate cancer; however, it is unclear as of 2022 whether they reduce any cases of dangerous disease. Treatment of prostate cancer varies based on how advanced

2014-415: Is a major topic of ongoing research. From 2016–2020, over $ 1.26 billion was invested in prostate cancer research, representing around 5% of global cancer research funds. This places prostate cancer 10th among 18 common cancer types in funding per cancer death, and 9th in funding per disability-adjusted life year lost. Research into prostate cancer relies on a number of laboratory models to test aspects of

2120-569: Is associated with variations in BRCA2 (up to an eight-fold increased risk) and HOXB13 (three-fold increased risk), both of which are involved in repairing DNA damage . Variants in other genes involved in DNA damage repair have also been associated with an increased risk of developing prostate cancer – particularly early-onset prostate cancer – including BRCA1 , ATM , NBS1 , MSH2 , MSH6 , PMS2 , CHEK2 , RAD51D , and PALB2 . Additionally, variants in

2226-523: Is awarded to authors for their work in inspiring children and improving their literacy. Rendell wrote two unpublished novels before the 1964 publication of From Doon with Death , which was purchased for £75 by John Long; it was the first mystery to feature Chief Inspector Reginald Wexford . Rendell said that the character of Wexford was based on herself. The Monster in the Box , released in October 2009,

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2332-524: Is best known for creating Chief Inspector Wexford . A second string of works was a series of unrelated crime novels that explored the psychological background of criminals and their victims. This theme was developed further in a third series of novels, published under the pseudonym Barbara Vine . Rendell was born as Ruth Barbara Grasemann in 1930, in South Woodford , Essex (now Greater London ). Her parents were teachers. Her mother, Ebba Kruse,

2438-510: Is caused by the accumulation of genetic mutations to the DNA of cells in the prostate. These mutations affect genes involved in cell growth, replication, cell death , and DNA damage repair . With these processes dysregulated, some cells replicate abnormally, forming a clump of cells called a tumor. As the tumor grows, its cells accumulate more mutations, allowing it to stimulate the growth of new blood vessels to support further growth. Eventually,

2544-412: Is done through blood tests to measure levels of the protein prostate-specific antigen (PSA), which are elevated in those with enlarged prostates, whether due to prostate cancer or benign prostatic hyperplasia . The typical man's blood has around 1 nanogram (ng) of PSA per milliliter (mL) of blood tested. Those with PSA levels below average are very unlikely to develop dangerous prostate cancer over

2650-711: Is more likely in those who are older or had previous erectile issues. Incontinence is more common in those who are older and have shorter urethras . Both for cancer progression outcomes and surgical side effects, the skill and experience of the individual surgeon doing the procedure are among the greatest determinants of success. After prostatectomy, PSA levels drop rapidly, reaching very low or undetectable levels within two months. Radiotherapy also substantially reduces PSA levels, but more slowly and less completely, with PSA levels reaching their nadir two years after radiotherapy. After either treatment, PSA levels are monitored regularly. Up to half of those treated will eventually have

2756-651: Is rare in regions with a low Human Development Index . Men suspected of having prostate cancer may undergo several tests to assess the prostate. One common procedure is the digital rectal examination , in which a doctor inserts a lubricated finger into the rectum to feel the nearby prostate. Tumors feel like stiff, irregularly shaped lumps against the rest of the prostate. Hardening of the prostate can also be due to benign prostatic hyperplasia ; around 20–25% of those with abnormal findings on their rectal exams have prostate cancer. Several urological societies' guidelines recommend magnetic resonance imaging (MRI) to evaluate

2862-412: Is the uncontrolled growth of cells in the prostate , a gland in the male reproductive system below the bladder . Abnormal growth of prostate tissue is usually detected through screening tests, typically blood tests that check for prostate-specific antigen (PSA) levels. Those with high levels of PSA in their blood are at increased risk for developing prostate cancer. Diagnosis requires a biopsy of

2968-414: Is the designation for any of three higher risk factors: IIIA is for a PSA level about 20 ng/mL; IIIB is for T3 or T4 tumors; IIIC is for a Gleason grade group of 5. Stage IV is for cancers that have spread to lymph nodes (N1, stage IVA) or other organs (M1, stage IVB). The United Kingdom National Institute for Health and Care Excellence recommends a five-stage system based on disease prognosis called

3074-423: Is the most advanced stage of the disease, called castration-resistant prostate cancer (CRPC). CRPC tumors continuously evolve resistance to treatments, necessitating several lines of therapy, each used in sequence to extend survival. The standard of care is the chemotherapy docetaxel along with antiandrogen drugs, namely the androgen receptor antagonists enzalutamide , apalutamide , and darolutamide , as well as

3180-455: Is unavailable, prostatectomy can be performed laparoscopically (using a camera and hand tools through small holes in the abdomen), or through traditional open surgery with an incision above the penis (retropubic approach) or below the scrotum (perineal approach). The four approaches result in similar rates of cancer control. Damage to nearby tissue during surgery can result in erectile dysfunction and urinary incontinence . Erectile dysfunction

3286-478: The BRCA2 gene. Each year 1.2 million cases of prostate cancer are diagnosed, and 350,000 die of the disease, making it the second-leading cause of cancer and cancer death in men. One in eight men is diagnosed with prostate cancer in his lifetime and one in forty dies of the disease. Prostate tumors were first described in the mid-19th century, during surgeries on men with urinary obstructions. Initially, prostatectomy

Erast Fandorin - Misplaced Pages Continue

3392-661: The Female Genital Mutilation Act 2003 (the intent was to prevent the practice). In August 2014, Rendell was one of 200 public figures who were signatories to a letter to The Guardian expressing their hope that Scotland would vote to remain part of the United Kingdom in September's referendum on that issue . Rendell was a vegetarian who was described as living mostly on fruit. She described herself as "slightly agoraphobic " and slept in

3498-574: The Wnt signaling pathway via disruption of members APC (9% of tumors) or CTNNB1 (4% of tumors); or dysregulation of the PI3K pathway via PI3KCA / PI3KCB mutations (6% of tumors) or AKT1 (2% of tumors). Prostate cancer is the second-most frequently diagnosed cancer in men, and the second-most frequent cause of cancer death in men (after lung cancer ). Around 1.2 million new cases of prostate cancer are diagnosed each year, and over 350,000 people die of

3604-424: The urine or semen , or trouble urinating – commonly including frequent urination and slow or weak urine stream. More than half of men over age 50 experience some form of urination problem, typically due to issues other than prostate cancer such as benign prostatic hyperplasia (non-cancerous enlargement of the prostate). Advanced prostate tumors can metastasize to nearby lymph nodes and bones, particularly in

3710-547: The Cambridge Prognostic Group, with prognostic groups CPG 1 to CPG 5. CPG 1 is the same as AJCC stage I. Cases with localized tumors (T1 or T2) and either Gleason grade group 2 or higher PSA levels (10 to 20 ng/mL) are designated CPG 2. CPG 3 represents either Gleason grade group 3, or the combination of the CPG 2 criteria. CPG 4 is similar to AJCC stage 3 – any of Gleason grade group 4, PSA levels above 20 ng/mL, or

3816-462: The DNA repair-related genes BRCA2 and ATM are rare in localized disease but found in at least 7% and 5% of metastatic disease cases respectively. The transition from castrate-sensitive to castrate-resistant prostate cancer is also accompanied by the acquisition of various gene mutations. In castrate-resistant disease, more than 70% of tumors have mutations in the androgen receptor signaling pathway – amplifications and gain-of-function mutations in

3922-520: The Fandorin series typically sell over 200,000 copies in the first week alone, with an unparalleled (for mystery novels) first edition of 50,000 copies for the first books to 500,000 copies for the last. The English translations of the novels have been critically acclaimed by, among others, Ruth Rendell . In the Soviet Union , detective novels enjoyed mass popularity. Although they were seen as

4028-467: The US Food and Drug Administration approved the systemic chemotherapy mitoxantrone for those with castration-resistant prostate cancer based on trials showing that it improved symptoms even though it failed to enhance survival. In 2004, docetaxel was approved as the first chemotherapy to increase survival in those with castration-resistant prostate cancer. After additional trials in 2015, docetaxel use

4134-418: The average person diagnosed at 67. The average age of those who die from prostate cancer is 77. Only a minority of prostate cancer cases are diagnosed. Autopsies of men who died at various ages have shown cancer in the prostates of over 40% of men over age 50. Incidence rises with age, and nearly 70% of men autopsied at age 80–89 had cancer in their prostates. Prostate cancer is more common in families with

4240-642: The cancer cells disrupt normal body function and continue to grow. Metastases cause most of the discomfort associated with prostate cancer, and can eventually kill the affected person. Most prostate tumors begin in the peripheral zone – the outermost part of the prostate. As cells begin to grow out of control, they form a small clump of disregulated cells called a prostatic intraepithelial neoplasia (PIN). Some PINs continue to grow, forming layers of tissue that stop expressing genes common to their original tissue location – p63 , cytokeratin 5 , and cytokeratin 14 – and instead begin expressing genes typical of cells in

4346-419: The cancer is, the risk it may spread, and the affected person's health and personal preferences. Those with localized disease at low risk for spread are often more likely to be harmed by the side effects of treatment than the disease itself, and so are regularly tested for a worsening of their disease. Those at higher risk may receive treatment to eliminate the tumor – typically prostatectomy (surgery to remove

Erast Fandorin - Misplaced Pages Continue

4452-691: The cancer's grade and stage at the time of diagnosis; those with lower stage disease have vastly improved prognoses. Around 80% of prostate cancer diagnoses are in men whose cancer is still confined to the prostate. These men can survive long after diagnosis, with as many as 99% still alive 10 years from diagnosis. Men whose cancer has metastasized to a nearby part of the body (around 15% of diagnoses) have poorer prognoses, with five-year survival rates of 60–80%. Those with metastases in distant body sites (around 5% of diagnoses) have relatively poor prognoses, with five-year survival rates of 30–40%. Those who have low blood PSA levels at diagnosis, and whose tumors have

4558-651: The coronation of Tsar Nicholas II and the Khodynka Tragedy for Coronation, or the Last of the Romanovs . Akunin uses the gaps in the knowledge of these histories to create an atmosphere for his mystery novels to which readers can relate. Ruth Rendell Ruth Barbara Rendell, Baroness Rendell of Babergh , CBE ( née   Grasemann ; 17 February 1930 – 2 May 2015) was an English author of thrillers and psychological murder mysteries. Rendell

4664-533: The detective novel in mind, from spies to serial killers. In addition, he wanted to address different types of human character in his books. As Akunin identified sixteen subgenres of crime novels, as well as sixteen character types, the novels in the Erast Fandorin series ultimately numbered sixteen, with the final novel, Not Saying Goodbye , published in 2018. The series is titled Новый детективъ ( New detective , or New Mystery ). This title serves to set

4770-461: The development of GnRH agonists, which were found to be as effective as estrogen without the increased risk of clotting. Schally was awarded the 1977 Nobel Prize in Physiology or Medicine for his work on GnRH and prostate cancer. Systemic chemotherapy for prostate cancer has been studied since the 1950s but clinical trials failed to show benefits in most people who receive the drugs. In 1996,

4876-469: The disease, annually. One in eight men are diagnosed with prostate cancer in their lifetime, and around one in forty die of the disease. Rates of prostate cancer rise with age. Due to this, prostate cancer rates are generally higher in parts of the world with higher life expectancy, which also tend to be areas with higher gross domestic product and higher human development index . Australia, Europe, North America, New Zealand, and parts of South America have

4982-468: The disease, called castration-resistant prostate cancer, is treated with continued hormone therapy alongside the chemotherapy drug docetaxel . Some tumors metastasize (spread) to other areas of the body, particularly the bones and lymph nodes . There, tumors cause severe bone pain , leg weakness or paralysis, and eventually death. Prostate cancer prognosis depends on how far the cancer has spread at diagnosis. Most men diagnosed have tumors confined to

5088-419: The disease. Several prostate immortalized cell lines are widely used, namely the classic lines DU145 , PC-3 , and LNCaP , as well as more recent cell lines 22Rv1, LAPC-4 , VCaP , and MDA-PCa-2a and −2b. Research requiring more complex models of the prostate uses organoids – clusters of prostate cells that can be grown from human prostate tumors or stem cells. Modeling tumor growth and metastasis requires

5194-597: The disease; however, detection of cancer cases that would not have otherwise impacted health can cause anxiety, and lead to unneeded biopsies and treatments, both of which can cause unwanted complications. Major national health organizations offer differing recommendations, attempting to balance the benefits of early diagnosis with the potential harms of treating people whose tumors are unlikely to impact health. Most medical guidelines recommend that men at high risk of prostate cancer (due to age, family history, ethnicity, or prior evidence of high blood PSA levels) be counseled on

5300-626: The end of their lives, most experience confusion and may hallucinate or have trouble recognizing loved ones. Confusion is caused by various conditions, including kidney failure , sepsis , dehydration , and as a side effect of various drugs, especially opioids . Most people sleep for long periods, and some feel drowsy when awake. Restlessness is also common, sometimes caused by physical discomfort from constipation or urinary retention , sometimes caused by anxiety. In their last few days, affected men's breathing may become shallow and slow, with long pauses between breaths. Breathing may be accompanied by

5406-401: The extent of disease, and was easier for surgeons to learn. This was improved upon by Patrick C. Walsh 's 1983 description of a retropubic prostatectomy approach that avoided damage to the nerves near the prostate, preserving erectile function. Radiation therapy for prostate cancer was used occasionally in the early 20th century, with radium implanted into the urethra or rectum to reduce

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5512-422: The extent of the tumor (T), spread to any lymph nodes (N), and the presence of metastases (M). Scores of T1 and T2 represent tumors that remain within the prostate: T1 is for tumors not detectable by imaging or digital rectal exam; T2 is for tumors detectable by imaging or rectal exam, but still confined within the prostate. T3 is for tumors that grow beyond the prostate – T3a for tumors with any extension outside

5618-660: The first author to be nominated and win under multiple names. Her unparalleled Edgar and Dagger finalist nominations include: A Judgement In Stone (1977 Gold Dagger finalist), A Sleeping Life (1979 Edgar finalist for Best Novel), Make Death Love Me (1980 Edgar finalist for Best Novel), The Speaker Of Mandarin (1983 Gold Dagger finalist), An Unkindness Of Ravens and The Tree Of Hands (both 1986 Edgar finalists for Best Novel), A Dark-Adapted Eye (as Barbara Vine, 1986 Gold Dagger finalist), A Fatal Inversion (as Barbara Vine, 1988 Macavity Award finalist for Best Novel), and Going Wrong (1990 Gold Dagger finalist.) Additionally, she

5724-512: The genome near the oncogene MYC are associated with increased risk. As are single-nucleotide polymorphisms in the vitamin D receptor common in African-Americans, and in the androgen receptor , CYP3A4 , and CYP17 involved in testosterone synthesis and signaling. Together, known gene variants are estimated to cause around 25% of prostate cancer cases, including 40% of early-onset prostate cancers. Men who are taller are at

5830-588: The hated Agatha (Christie) and that awful Marple woman ; and says of St. Mary Mead that she can hardly bear to say the name of that village where one finds a lot of normal, law-abiding people living ordinary, blameless lives, who suddenly decide to murder their aunt. Well, I don't believe that. ( Introducing Chief Inspector Wexford by Daniel Mallory; from 1990 Rendell interview with Marilyn Stasio ) In addition to these police procedurals starring Wexford, Rendell wrote psychological crime novels exploring such themes as romantic obsession, misperceived communication,

5936-453: The highest incidence. South Asia, Central Asia, and sub-Saharan Africa have the lowest incidence of prostate cancer; though incidence is increasing quickly in these regions. Prostate cancer is the most diagnosed cancer in men in over half of the world's countries, and the leading cause of cancer death in men in around a quarter of countries. Prostate cancer is rare in those under 40 years old, and most cases occur in those over 60 years, with

6042-526: The impact of chance and coincidence, and the humanity of the criminals involved. Among such books are A Judgement in Stone , The Face of Trespass , Live Flesh , Talking to Strange Men , The Killing Doll , Going Wrong and Adam and Eve and Pinch Me . For the last novel published in her lifetime, The Girl Next Door , she returned to the Loughton of her childhood, with an implied comparison of

6148-504: The innermost lining of the pancreatic duct – cytokeratin 8 and cytokeratin 18 . These multilayered PINs also often overexpress the gene AMACR , which is associated with prostate cancer progression. Some PINs can eventually grow into tumors. This is commonly accompanied by large-scale changes to the genome , with chromosome sequences being rearranged or copied repeatedly. Some genomic alterations are particularly common in early prostate cancer, namely gene fusion between TMPRSS2 and

6254-486: The likelihood that a person will develop aggressive prostate cancer. Many measure "free PSA" – the fraction of PSA unbound to other blood proteins, usually around 10% to 30%. Men who have a lower percentage of free PSA are more likely to have prostate cancer. Several common tests more accurately detect prostate cancer cases by also measuring subtypes of free PSA, including the Prostate Health Index (measures

6360-402: The moral climate of wartime England and 2014. Rendell created a third strand of writing with the publication in 1986 of A Dark-Adapted Eye under her pseudonym Barbara Vine (the name was derived from her own middle name and her great-grandmother's maiden name). King Solomon's Carpet , A Fatal Inversion and Asta's Book (alternative U.S. title, Anna's Book ), among others, inhabited

6466-401: The more severe Gleason score (4) covered more area. A score of 8 is grade group 4. A score of 9 or 10 is grade group 5 (worst prognosis). The extent of cancer spread is assessed by MRI or PSMA scan – a positron emission tomography (PET) imaging technique where a radioactive label that binds the prostate protein prostate-specific membrane antigen is used to detect metastases distant from

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6572-415: The most severely cancerous. Gleason scores are commonly grouped into "Gleason grade groups", which predict disease prognosis: a Gleason score of 6 is Gleason grade group 1 (best prognosis). A score of 7 (with Gleason scores 4 + 3, or Gleason scores 3 + 4, with the most prominent listed first) can be grade group 2 or 3; it is grade group 2 if the less severe Gleason score (3) covered more area; grade group 3 if

6678-781: The next 8 to 10 years. Men with PSA levels above 4 ng/mL are at increased risk – around 1 in 4 will develop prostate cancer – and are often referred for a prostate biopsy. PSA levels over 10 ng/mL indicate an even higher risk: over half of men in this group develop prostate cancer. Men with high PSA levels are often recommended to repeat the blood test four to six weeks later, as PSA levels can fluctuate unrelated to prostate cancer. Benign prostatic hyperplasia , prostate infection , recent ejaculation , and some urological procedures can increase PSA levels; taking 5α-reductase inhibitors can decrease PSA levels. Those with elevated PSA may undergo secondary screening blood tests that measure subtypes of PSA and other molecules to better predict

6784-412: The next few months. With either technique, radiation damage to nearby organs can increase the risk of subsequent bladder cancer and cause erectile dysfunction , infertility , irreversible lumbar plexopathy and radiation proctitis – damage to the rectum that can cause diarrhea , bloody stools , fecal incontinence , and pain. Radical prostatectomy aims to surgically remove the cancerous part of

6890-415: The novels and she always wrapped them in brown paper to prevent people from seeing what she was reading. This inspired Akunin to create a detective novel which nobody would be ashamed to be caught reading, something between the literature of Leo Tolstoy and Fyodor Dostoevsky and the pulp of modern Russian detective novels. He set out to write a cycle about Fandorin with an exploration of every subgenre of

6996-555: The novels apart from the postmodernist intellectual novels as well as from the trashy detective novels, but it is also a subtle play on the use of time in the novels. Akunin uses many historical settings for his novels. He uses the war between Russia and the Ottoman Empire as background for the novel The Turkish Gambit ; the death of the "White General" Mikhail Skobelev (as 'Mikhail Sobolev') in The Death of Achilles ; and

7102-502: The oncogene ERG (up to 60% of prostate tumors), mutations that disable SPOP (up to 15% of tumors), and mutations that hyperactivate FOXA1 (up to 5% of tumors). Metastatic prostate cancer tends to have more genetic mutations than localized disease. Many of these mutations are in genes that protect from DNA damage, such as p53 (mutated in 8% of localized tumors, more than 27% of metastatic ones) and RB1 (1% of localized tumors, more than 5% of metastatic ones). Similarly mutations in

7208-410: The pathologist assigns numbers ranging from 3 (most similar to healthy prostate tissue) to 5 (least similar) to different regions of the biopsied tissue. They then calculate a "Gleason score" by adding the two numbers that represent the largest areas of the biopsy sample. The lowest possible Gleason score of 6 represents a biopsy most similar to healthy prostate; the highest Gleason score of 10 represents

7314-537: The pelvis, hips, spine, ribs, head, and neck. There they can cause fatigue , unexplained weight loss, and back or bone pain that does not improve with rest. Metastases can damage the bones around them, and around a quarter of those with metastatic prostate cancer develop a bone fracture . Growing metastases can also compress the spinal cord causing weakness in the legs and feet, or limb paralysis. Most cases of prostate cancer are diagnosed through screening tests, when tumors are too small to cause any symptoms. This

7420-614: The primary cause of symptoms and death from metastatic prostate cancer. Those with constant pain are prescribed nonsteroidal anti-inflammatory drugs . However, people with bone metastases can experience "breakthrough pain", sudden bursts of severe pain that resolve within around 15 minutes, before pain medications can take effect. Single sites of pain can be treated with external beam radiation therapy to shrink nearby tumors. More dispersed bone pain can be treated with radioactive compounds that disproportionately accumulate in bone, like radium-223 and samarium-153-EDTMP , which help reduce

7526-501: The prostate are often impossible in women who have undergone vaginoplasty , as the length and rigidity of the new vagina can obstruct access to the prostate from the rectum. A prostate mass was first described in 1817 by the English surgeon George Langstaff , following the autopsy of a man who had died at age 68 with lower-body pain and urinary issues. In 1853, London Hospital surgeon John Adams described another prostate tumor from

7632-402: The prostate for potential tumors in men with high PSA levels. MRI results can help distinguish those who have potentially dangerous tumors from those who do not. A definitive diagnosis of prostate cancer requires a biopsy of the prostate. Prostate biopsies are typically taken by a needle passing through the rectum or perineum , guided by transrectal ultrasonography , MRI, or a combination of

7738-425: The prostate with relatively little radiation to other organs, or by brachytherapy , where a radioactive source is surgically inserted into the prostate. IMRT is given over several sessions, with treatments repeated five days per week for several weeks. Brachytherapy is typically performed in a single session, with the radioactive source permanently implanted into the prostate, where it expends its radioactivity within

7844-802: The prostate) or radiation therapy , sometimes alongside hormone therapy . Those with metastatic disease are treated with chemotherapy , as well as radiation or other agents to alleviate the symptoms of metastatic tumors. Blood PSA levels are monitored every few months to assess the effectiveness of treatments, and whether the disease is recurring or advancing. Men diagnosed with low-risk cases of prostate cancer often defer treatment and are monitored regularly for cancer progression by active surveillance , which involves testing for tumor growth at fixed intervals by PSA tests (around every six months), digital rectal exam (annually), and MRI or repeat biopsies (every one to three years). This program continues until increases in PSA levels, Gleason grade, or tumor size indicate

7950-495: The prostate, along with the seminal vesicles, and the end of the vas deferens (the duct that delivers sperm from the testes). In wealthier countries, this is typically done by robot-assisted surgery , where robotic tools inserted through small holes in the abdomen allow a surgeon to make small and exact movements during surgery. This method results in shorter hospital stays, less blood loss, and fewer complications than traditional open surgery. In places where robot-assisted surgery

8056-492: The prostate. CT scans may also be used, but are less able to detect spread outside the prostate than MRI. Bone scintigraphy is used to test for spread of cancer to bones. After diagnosis, the tumor is staged to determine the extent of its growth and spread. Prostate cancer is typically staged using the American Joint Committee on Cancer 's (AJCC) three-component TNM system , with scores assigned for

8162-567: The prostate. If cancer is present, the pathologist assigns a Gleason score , and a higher score represents a more dangerous tumor. Medical imaging is performed to look for cancer that has spread outside the prostate. Based on the Gleason score, PSA levels, and imaging results, a cancer case is assigned a stage 1 to 4. A higher stage signifies a more advanced, more dangerous disease. Most prostate tumors remain small and cause no health problems. These are managed with active surveillance , monitoring

8268-434: The prostate; 99% of them survive more than 10 years from their diagnoses. Tumors that have metastasized to distant body sites are most dangerous, with five-year survival rates of 30–40%. The risk of developing prostate cancer increases with age; the average age of diagnosis is 67. Those with a family history of any cancer are more likely to have prostate cancer, particularly those who inherit cancer-associated variants of

8374-867: The prostate; T3b for tumors that invade the adjacent seminal vesicles . T4 is for tumors that have grown into organs beyond the seminal vesicles. The N and M scores are binary (yes or no). N1 represents any spread to the nearby lymph nodes. M1 represents any metastases to other body sites. The AJCC then combines the TNM scores, Gleason grade group, and results of the PSA blood test to categorize cancer cases into one of four stages, and their subdivisions. Cancer cases with localized tumors (T1 or T2), no spread (N0 and M0), Gleason grade group 1, and PSA less than 10 ng/mL are designated stage I. Those with localized tumors and PSA between 10 and 20 ng/mL are designated stage II – subdivided into IIA for Gleason grade group 1, IIB for grade group 2, and IIC for grade group 3 or 4. Stage III

8480-487: The receptor gene itself, amplification of its activators (for example, FOXA1), or inactivating mutations in its negative regulators (for example, ZBTB16 and NCOR1 ). These androgen receptor disruptions are only found in up to 6% of biopsies of castrate-sensitive metastatic disease. Similarly, deletions of the tumor suppressor PTEN are harbored by 12–17% of castrate-sensitive tumors, but over 40% of castrate-resistant tumors. Less commonly, tumors have aberrant activation of

8586-420: The removed prostate tissue. Two studies around the time found cancer in as many as 10% of surgical specimens, suggesting prostate cancer was a fairly common cause of prostate enlargement. For much of the 20th century, the primary therapy for prostate cancer was surgery to remove the prostate. Perineal prostatectomy was first performed in 1904 by Hugh H. Young at Johns Hopkins Hospital . Young's method became

8692-409: The rest largely squamous-cell carcinoma (resembling squamous cells , a type of epithelial cell ) and transitional cell carcinoma (resembling transitional cells ). Next, tumor samples are graded based on how much the tumor tissue differs from normal prostate tissue; the more different the tumor appears, the faster the tumor is likely to grow. The Gleason grading system is commonly used, where

8798-534: The risks and benefits of PSA testing, and be offered access to screening tests. Medical guidelines generally recommend against screening for men over age 70, or with a life expectancy of less than 10 years, as a newly diagnosed prostate cancer is unlikely to impact their natural lifespan. Uptake of screening varies by geography – more than 80% of men are screened in the US and Western Europe, 20% of men in Japan, and screening

8904-469: The same territory as her psychological crime novels while further developing themes of human misunderstandings and the unintended consequences of family secrets and hidden crimes. The author was noted for her elegant prose and sharp insights into the human mind, as well as her cogent plots and characters. Rendell injected the social changes of the last 40 years into her work, bringing awareness to such issues as domestic violence . The Inspector Wexford series

9010-456: The size of bone tumors. Similarly, the systemic chemotherapeutics used for metastatic prostate cancer can reduce pain as they shrink tumors. Other bone modifying agents like zoledronic acid and denosumab can reduce prostate cancer bone pain, even though they have little effect on tumor size. Metastases compress the spinal cord in up to 12% of those with metastatic prostate cancer causing pain, weakness, numbness, and paralysis. Inflammation in

9116-622: The spine can be treated with high-dose steroids, as well as surgery and radiotherapy to shrink spinal tumors and relieve pressure on the spinal cord. Those with advanced prostate cancer suffer fatigue, lethargy, and a generalized weakness. This is caused in part by gastrointestinal problems, with loss of appetite , weight loss, nausea, and constipation all common. These are typically treated with appetite-increasing drugs – megestrol acetate or corticosteroids – antiemetics , or treatments that focus on underlying gastrointestinal issues. General weakness can also be caused by anemia , itself caused by

9222-1063: The synthesis or action of testosterone , the primary androgen. The first line of treatment typically involves GnRH agonists like leuprolide , goserelin , or triptorelin by injection monthly or less frequently as needed. GnRH agonists cause a brief rise in testosterone levels at treatment initiation, which can worsen disease in people with significant symptoms of metastases. In these people, GnRH antagonists like degarelix or relugolix are given instead, and can also rapidly reduce testosterone levels. Reducing testosterone can cause various side effects, including hot flashes , reduction in muscle mass and bone density, reduced sex drive, fatigue, personality changes, and an increased risk of diabetes, cardiovascular disease, and depression. Hormone therapy halts tumor growth in more than 95% of those treated, and PSA levels return to normal in up to 70%. Despite reduced testosterone levels, metastatic prostate tumors eventually continue to grow – manifested by rising blood PSA levels, and metastases to nearby bones. This

9328-459: The testosterone production inhibitor abiraterone acetate . An alternative is the cell therapy procedure Sipuleucel-T , where the affected person's immune cells are removed, treated to more effectively target prostate cancer cells, and re-injected. Tumors that evolve resistance to docetaxel may receive the second-generation taxane drug cabazitaxel . Some CRPC treatments are used only in men whose tumors have certain characteristics that make

9434-534: The therapy more likely to be effective. Men whose tumors express the protein PSMA may receive the radiopharmaceutical Lu-177 PSMA , which binds to and destroys PSMA-positive cells. Those whose tumors have defective DNA damage repair benefit from treatment with the immune checkpoint inhibitor drug pembrolizumab and PARP inhibitors, namely olaparib , rucaparib , or niraparib . Bone metastases – present in around 85% of those with metastatic prostate cancer – are

9540-400: The tumor size and associated symptoms. In the 1950s the advent of more powerful radiation machines allowed for external beam radiotherapy to reach the prostate. By the 1960s, this was often combined with hormone therapy to improve the potency of therapy. In the 1970s, Willet Whitmore pioneered an open surgery technique where needles of Iodine-125 were placed directly into the prostate. This

9646-452: The tumor with regular tests to ensure it has not grown. Tumors more likely to be dangerous can be destroyed with radiation therapy or surgically removed by radical prostatectomy . Those whose cancer spreads beyond the prostate are treated with hormone therapy which reduces levels of the androgens (male sex hormones) that prostate cells need to survive. Eventually cancer cells can grow resistant to this treatment. This most-advanced stage of

9752-500: The two. Ten to twelve samples are taken from several regions of the prostate to improve the chances of finding any tumors. Biopsies are sent for a histopathologic diagnosis of prostate cancer , wherein they are examined under a microscope by a pathologist , who determines the type and extent of cancerous cells present. Cancers are first classified based on their appearance under a microscope. Over 95% of prostate cancers are classified as adenocarcinomas (resembling gland tissue), with

9858-401: The widespread standard, initially done primarily to relieve symptoms of urinary blockage. In 1931 a new surgical method, transurethral resection of the prostate , became available, replacing perineal prostatectomy for symptomatic relief of obstruction. In 1945, Terence Millin described a retropubic prostatectomy approach, which provided easier access to pelvic lymph nodes to assist in staging

9964-417: Was 20, and in 1953 had a son, Simon, now a psychiatrist -social worker who lives in the U.S. state of Colorado. The couple divorced in 1975 but remarried two years later. Don Rendell died in 1999 from prostate cancer . She made the county of Suffolk her home for many years, using the settings in several of her novels. She lived in the villages of Polstead and later Groton , both east of Sudbury . She

10070-789: Was also a patron of the charity Kids for Kids which helps children in rural areas of Darfur . There is a blue plaque on one of her homes, 45 Millsmead Way, in Loughton . This was unveiled by her son Simon on 24 February 2016. Four of her novels appear on the British-based Crime Writers Association Poll (1990) of the best crime fiction novels ever written: two under the Rendell name and two under her pen name of Barbara Vine. Her Crime Writer’s Association Dagger wins (four Gold, one Silver and one Cartier Diamond) remains unmatched, as does her record of being

10176-752: Was appointed a Commander of the Order of the British Empire (CBE) in the 1996 Birthday Honours and a life peer as Baroness Rendell of Babergh , of Aldeburgh in the County of Suffolk, on 24 October 1997. She sat in the House of Lords for the Labour Party . In 1998, Rendell was named in a list of the party's biggest private financial donors. She introduced into the Lords the bill that would later become

10282-403: Was awarded the 1966 Nobel Prize in Physiology or Medicine for this discovery, the first systemic therapy for prostate cancer. In the 1960s, large studies showed estrogen therapy to be as effective as surgical castration at treating prostate cancer, but that those on estrogen therapy were at increased risk of suffering blood clots . Through the 1980s, Andrzej W. Schally 's studies of GnRH led to

10388-511: Was based on Rendell's short story of the same name. Two episodes of Tales of the Unexpected were based on Rendell's short stories - "A Glowing Future" ( series 4 , episode 15) and "People Don't Do Such Things" ( series 8 , episode 1). A critical essay on Rendell's crime novels appears in S. T. Joshi 's book Varieties of Crime Fiction (Wildside Press, 2019) ISBN   978-1-4794-4546-2 . Prostate cancer Prostate cancer

10494-745: Was born in Sweden to Danish parents and brought up in Denmark; her father, Arthur Grasemann, was English. As a result of spending Christmas and other holidays in Scandinavia, Rendell learned Swedish and Danish. Rendell was educated at the County High School for Girls in Loughton , Essex, the town to which the family moved during her childhood. In 2016 a blue plaque was unveiled at her former home, 45 Millsmead Way, Loughton, in recognition of her time living there. After high school, she became

10600-510: Was extended to those with castration-sensitive prostate cancer. Prostate cancer screening and awareness have been widely promoted since the early 2000s by Prostate Cancer Awareness Month in September and Movember in November. However, an analysis of internet searches suggests neither event changes the level of prostate cancer interest or discussion much, in contrast to the more established Breast Cancer Awareness Month . Prostate cancer

10706-691: Was improved upon by Henrik H. Holm in 1983 by using transrectal ultrasound to guide the implantation of radioactive material. The observation that the testicles (and the hormones they secrete) influence prostate size was made as early as the late 18th century via castration experiments in animals. However, occasional experimentation over the next century bore mixed results, likely due to the inability to separate prostate tumors from prostates enlarged due to benign prostatic hyperplasia. In 1941, Charles B. Huggins and Clarence V. Hodges published two studies using surgical castration or oral estrogen to reduce androgen levels and improve prostate cancer symptoms. Huggins

10812-633: Was nominated four times in the Edgar Best Short Story category (in 1976 for "The Fall Of The Coin" and 1977 for "People Don’t Do Such Things"), winning twice for "The Fallen Curtain" (1975) and "The New Girlfriend" (1984). Rendell suffered a stroke on 7 January 2015, and she died on 2 May at St George's Hospital in Tooting , London. The Ruth Rendell Award was introduced in 2016 by the National Literacy Trust . It

10918-729: Was one of the few film adaptations of her work that she was happy with. The novel was also filmed in 1986 with Rita Tushingham . Chabrol made La Demoiselle d'honneur in 2004, based on The Bridesmaid . Other adaptations are Diary of the Dead (1976), from the book One Across, Two Down ; the 1997 Pedro Almodóvar film Live Flesh ; The Tree of Hands , directed by Giles Foster for Granada with Lauren Bacall (U.S. title: "Innocent Victim"); and another version of The Tree of Hands , Betty Fisher et autres histoires (2001, a.k.a. Alias Betty ), with screenplay and direction by Claude Miller . François Ozon's 2015 film The New Girlfriend

11024-544: Was successfully televised, starring George Baker as Inspector Wexford and Christopher Ravenscroft as Detective Mike Burden, under the title The Ruth Rendell Mysteries , with 48 episodes from 1987 to 2000. Rendell praised Baker's performance, stating "It was a marvellous achievement as an actor to make him more and better than the author intended." Many of her other works have been adapted for film and television. She said that Claude Chabrol 's 1995 version of A Judgement in Stone , La Cérémonie with Sandrine Bonnaire ,

11130-453: Was the primary treatment for prostate cancer. By the mid-20th century, radiation treatments and hormone therapies were developed to improve prostate cancer treatment. The invention of hormone therapies for prostate cancer was recognized with the 1966 Nobel Prize to Charles B. Huggins and the 1977 Prize to Andrzej W. Schally . Early prostate cancer usually causes no symptoms. As the cancer advances, it may cause erectile dysfunction , blood in

11236-452: Was widely suggested to be Wexford's last case. This was incorrect; however it was the final novel featuring Wexford as an employed policeman. In the two following novels, The Vault and No Man's Nightingale , he was retired but was still involved in police investigations as a "consultant". In Introducing Chief Inspector Wexford by Daniel Mallory he says (based on a 1990 interview with Rendell by Marilyn Stasio ) that Rendell refers to

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